Implantable device containing GDNF secreting cells for treating nerve damage and methods of use

Abstract

A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process. An implantable device containing recombinant GDNF secreting cells encapsulated in a semipermeable membrane may be used to treat nerve damage in patients suffering from disorders such as Parkinson's disease.

We claim: 
     
       1. A device for treating nerve damage by implantation in a patient comprising: a membrane, and   one or more cells modified to express and secrete glial cell line-derived neurotrophic factor encapsulated within said membrane, provided however, said one or more cells are not B49 glioblastoma cells,   wherein said membrane is permeable to said glial cell line-derived neurotrophic factor, and impermeable to immune system materials from said patient which are detrimental to said cells, and   wherein said glial cell line-derived neurotrophic factor is a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:4 or SEQ ID NO:6 or a polypeptide which is at least 70% identical to an amino acid sequence set forth in SEQ ID NO:4 or SEQ ID NO:6 when four gaps in a length of 100 amino acids may be introduced to assist in that alignment, and wherein said glial cell line-derived neurotrophic factor has the ability to promote the survival or function of nerve cells.   
     
     
       2. The device of claim 1 wherein said cells contain an expression regulatory element operatively linked to a nucleic acid sequence encoding said glial cell line-derived neurotrophic factor. 
     
     
       3. The device of claim 1 wherein said glial cell line-derived neurotrophic factor comprises a polypeptide which is at least 70% identical to an amino acid sequence set forth in SEQ ID NO:4 OR SEQ ID NO:6 when four gaps in a length of 100 amino acids may be introduced to assist in that alignment. 
     
     
       4. The device of claim 1 wherein said glial cell line-derived neurotrophic factor comprises the amino acid sequence of SEQ ID NO:6. 
     
     
       5. A device for treating nerve damage by implantation in a patient, comprising: a membrane; and   one or more cells contained within said membrane, wherein said cells express and secrete a glial cell line-derived neurotrophic factor comprising the amino acid sequence set forth in SEQ ID NO:6, provided however, said one or more cells are not B49 glioblastoma cells, and   wherein said membrane is permeable to said glial cell line-derived neurotrophic factor.   
     
     
       6. The device of claim 5, wherein said membrane is suitable for implantation in the central nervous system of the patient. 
     
     
       7. A method for treating nerve damage comprising implanting a device according to claims 1 or 5 into a patient in need thereof. 
     
     
       8. The method of claim 7 wherein said patient is suffering from Parkinson's disease. 
     
     
       9. The method of claim 7 wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:6.